Expression of a novel pyridoxal kinase mRNA splice variant,PKH-T, in human testis

Aim: To identify the genes specifically expressed in human adult and fetal testes and spermatozoa. Methods: A human testis cDNA microarray was established. Then mRNAs of human adult and fetal testis and spermatozoa were purified and probes were prepared by a reverse transcription reaction with mRNA as the template. The microarray was hybridized with probes of adult and fetal testes and spermatozoa. The nucleic acid sequences of differentially expressed genes were determined and homologies were searched in the databases of GenBank. Results: A novel human testis-specific gene, PKH-T, was identified by hybridizing adult and fetal testis and spermatozoa probes with a human testis cDNA microarray. The cDNA of PKH-T was 1 069 bp in length. The cDNA sequence of this clone was deposited in the Genbank (AY303972) and PKH-T was also determined as Interim GenSymbol (Unigene, HS.38041). PKH-T contained most PKH conserved motif. The 239 amino acid sequences deduced from the 719 bp open reading frame (ORF) had a homology with the gene PKH (U89606). PKH-T was specifically and strongly expressed in the testis. Comparison of the differential expressions of PKH and PKH-T in testes of different develop-mental stages indicated that PKH-T was expressed in the adult testis and spermatozoa, while PKH, in the adult, fetal and aged testes. PKH-T had no expression in the testis of Sertoli cell only and partially spermatogenic arrest patients. Conclusion: PKH-T is a gene highly expressed in adult human testis and spermatozoa. It may play an important role in spermatogenesis and could be related to male infertility. (Asian J Androl 2004 Jun; 6: 83-91)

Study of Preparation and Characteristics of Pyridoxalated Polyhemoglobin

ＳｔｕｄｙｏｆＰｒｅｐａｒａｔｉｏｎａｎｄＣｈａｒａｃｔｅｒｉｓｔｉｃｓｏｆＰｙｒｉｄｏｘａｌａｔｅｄ ＰｏｌｙｈｅｍｏｇｌｏｂｉｎＬｉａｎｇＳｈｕｇｕａｎｇ；ＴｏｎｇＭｉｎｇｒｏｎｇ；ＰａｎＪｉｌｕｎａｎｄＹｕＹａｏｔｉｎｇ（Ｉｎｓｔｉｔｕｔｅｆｏ...

Pyridoxal 5'-phosphate alleviates prenatal pyridaben exposureinduced anxiety-like behaviors in offspring

Pyridaben(PY)is a widely used organochlorine acaricide,which can be detected in the peripheral blood of pregnant women.Available evidence suggests that PY has reproductive toxicity.However,it remains uncertain whether prenatal PY exposure impacts neurobehavioral development in offspring.Here,we administered PY to pregnant mice at a dose of 0.5 and 5 mg kg^(-1)day^(-1)via gavage and observed anxietylike behaviors in PY offspring aged five weeks.We then integrated the metabolome and transcriptome of the offspring's brain to explore the underlying mechanism.Metabolome data indicated that the vitamin B6 metabolism pathway was significantly affected,and the pyridoxal 50-phosphate(PLP)concentration and the active form of vitamin B6 was significantly reduced.Moreover,the transcriptome data showed that both PLP generation-related Pdxk and anxiety-related Gad1 were significantly down-regulated.Meanwhile,there was a decreasing trend in the concentration of GABA in the hippocampal DG region.Next,we supplemented PLP at a dose of 20 mg kg^(-1)day^(-1)to the PY offspring via intraperitoneal injection at three weeks.We found up-regulated expression of Pdxk and Gad1 and restored anxiety-like behaviors.This study suggests that prenatal exposure to PY can disrupt vitamin B6 metabolism,reduce the concentration of PLP,down-regulate the expression levels of Pdxk and Gad1,inhibit the production of GABA,and ultimately lead to anxiety-like behaviors in offspring.

Biomimetic Chiral Pyridoxal and Pyridoxamine Catalysts

What is the most favorite and original chemistry developed in your research group? Vitamin B6-based biomimetic asymmetric catalysis. How do you get into this specific field? Could you please share some experiences with our readers? Enzymatic transformations are characterized by high efficiency, specific selectivities, and mild conditions, which attracts me to do some chemistry related to biological systems.

Huoxue Rongluo Tablet reduces matrix metalloproteinase-9 expression in infarcted brain tissue

Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3：2：6：2：3：3：3：3. Huoxue Rongluo Tablet is a well-established and common pre- scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat- ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression.

Vitamin B6 and colorectal cancer:Current evidence and future directions

Colorectal cancer remains the third most common cancer in both women and men worldwide.Identifying modifiable dietary factors is crucial in developing primary prevention strategies.Vitamin B6 is involved in more than 100 coenzyme reactions,and may influence colorectal cancer risk in multiple ways including through its role in one-carbon metabolism related DNA synthesis and methylation and by reducing inflammation,cell proliferation,and oxidative stress.Observational studies of dietary or dietary plus supplementary intake of vitamin B6 and colorectal cancer risk have been inconsistent with most studies reporting nonsignificant positive or inverse associations.However,published studies of plasma pyridoxal 5'-phosphate(the active form of vitamin B6) levels consistently support an approximately 30%-50% reduction in risk of colorectal cancer comparing high with low concentrations.The reasons for the discrepancy in the results between dietary-based and plasma-based studies remain unresolved.Other unresolved questions include the effects of vitamin B6 intake in early life(i.e.,childhood or adolescence) and of suboptimal vitamin B6 status on colorectal cancer risk,whether the associations with vitamin B6 differ across molecular subtypes of colorectal cancer,and whether the vitamin B6-colorectal cancer association is modified by genetic variants of one-carbon metabolism.

Interactions and Effects on Cysteine Synthase Activity of Aminooxyacetate and Boc-Aminooxyacetate on the Bioherbicides <i>Colletotrichum truncatum</i>and <i>Alternaria cassia</i>and Their Weed Hosts

Aminooxyacetate (AOA) is a pyridoxal phosphate antagonist that inhibits various plant enzymes (including transaminases) which require pyridoxal phosphate as a cofactor and it exhibits phytotoxic and herbicidal properties. We examined AOA and its analog, N-t-butoxycarbonyl-AOA (Boc-AOA) for phytotoxicity, interactions with weed pathogens (bioherbicides), and effects on an important pyridoxal requiring enzyme, cysteine synthase (CS, E.C. 4.2.99.8). Studies were performed on two weeds, i.e., hemp sesbania [Sesbania exaltata (Raf.) Rybd. Ex A.W. Hill] and sicklepod (Senna obtusifolia), and two pathogens, (Colletotrichum truncatum and Alternaria cassiae), that are bioherbicidal agents against hemp sesbania and sicklepod, respectively. Pathogenicity tests, and assays for extractable, and in vitro CS activities were utilized. Phytotoxicity bioassays indicated that the bulky t-butoxycarbonyl moiety substitution on the AOA molecule did not substantially hinder expression of biological activity of Boc-AOA in these tests. Generally, spray application of the compounds to young dark-grown seedlings caused little growth effects, but root-feeding of the chemicals reduced growth (stem elongation) in both weeds. Hemp sesbania was generally more tolerant than sicklepod to these compounds. The only apparent positive interaction of the chemicals with these pathogens was the Boc-AOA: C. truncatum combination treatment on hemp sesbania. Both compounds reduced extractable CS in the seedlings by 30%, 72 h after treatment. CS activity was reduced by 15% in hemp sesbania treated with C. truncatum but increased 20% above control levels after infection of sicklepod by A. cassiae. This latter effect suggests that CS may be involved in sicklepod defense mechanisms against this pathogen.

The bacterial effector AvrRxo1 inhibits vitamin B6 biosynthesis to promote infection in rice

Xanthomonas oryzae pv.oryzicola(Xoc),which causes rice bacterial leaf streak,invades leaves mainly through stomata,which are often closed as a plant immune response against pathogen invasion.How Xoc overcomes stomatal immunity is unclear.Here,we show that the effector protein AvrRxo1,an ATPdependent protease,enhances Xoc virulence and inhibits stomatal immunity by targeting and degrading rice OsPDX1(pyridoxal phosphate synthase),thereby reducing vitamin B6(VB6)levels in rice.VB6 is required for the activity of aldehyde oxidase,which catalyzes the last step of abscisic acid(ABA)biosynthesis,and ABA positively regulates rice stomatal immunity against Xoc.Thus,we provide evidence supporting a model in which a major bacterial pathogen inhibits plant stomatal immunity by directly targeting VB6 biosynthesis and consequently inhibiting the biosynthesis of ABA in guard cells to open stomata.Moreover,AvrRxo1-mediated VB6 targeting also explains the poor nutritional quality,including low VB6 levels,of Xoc-infected rice grains.

A specialized role played by a redox cofactor

The redox cofactor𝛽-nicotinamide adenine dinucleotide(NAD)has been revealed to serve as a building block for the biosynthesis of an alkaloid natural product,altemicidin.The biosynthetic pathway investigation identified a unique pyridoxal pyrophosphate(PLP)-dependent enzyme that utilizes NAD and S-adenosylmethionine(SAM)to build the bicyclic alkaloid scaffold,opening the door for biosynthetic studies of NAD-derived natural products.